This proposal outlines a 5-year career development plan and research strategy through which the Candidate will bolster her clinical epidemiology expertise with implementation and behavioral science research capacity and develop and pilot an intervention for HIV-1 risk reduction among African HIV-1 serodiscordant couples desiring to conceive a child. Career development plan. As an Epidemiology PhD student, the Candidate became internationally recognized for her work on hormonal contraception and HIV-1 risk and the use of sophisticated statistical methods to address questions at the interface of HIV-1 prevention and reproductive health. The Candidate also used mixed-methods to explore the willingness of HIV-1 serodiscordant couples to use antiretrovirals for HIV-1 prevention and the results from this study have pushed the HIV-1 prevention field to consider how best to implement this new prevention strategy. The Candidate is currently a post-doctoral fellow at the University of Washington working with Dr. Jared Baeten. Dr. Baeten will serve as her primary mentor during K99 phase and a mentoring team with expertise in implementation science, behavioral science, reproductive health, qualitative data analysis, HIV-1 prevention clinical trial operations, antiretroviral adherence measurement and analysis, and biostatistics has been assembled to provide career guidance, ensure the establishment of research independence and the success of the research project. Through coursework, tutorials and seminars during the K99 phase, the Candidate will acquire skills enabling her to design interventions that are efficient and feasible, understand how to conduct monitoring and evaluation to improve intervention effectiveness, and learn from an iterative development process to ensure scalability and maximum applicability. These new skills will allow her to establish a research niche in effectiveness evaluations of reproductive health and HIV-1 prevention interventions. In the short term, her goals are to address questions aiming to reduce HIV-1 risk when couples desire fertility, how pregnancy or hormonal contraception may influence HIV-1 risk and/or disease progression, or best practices to promote long term HIV-1 risk reduction, including the implementation of antiretrovirals for HIV-1 prevention. Her long term goals are to pursue studies of multi-purpose prevention tools that have high efficacy to prevent pregnancy and HIV-1 infection. An enriching institutional environment at the Department of Global Health and the International Clinical Research Center within the University of Washington will support her career advancement. Research plan. There is a critical need for a risk reduction intervention for HIV-1 serodiscordant couples with fertility desires that is relevant for low-resource settings. Heterosexual HIV-1 serodiscordant partnerships, i.e. where one partner is HIV-1 infected and the other uninfected, face a difficult dilemma when considering their desire to have children: forego condom use and attempt to conceive but risk HIV-1 transmission or continue condom use and relinquish childbearing desires. Currently, many African couples choose to conceive despite the HIV-1 transmission risk and without knowledge of methods to reduce their HIV-1 risk. Antiretrovirals, when used as antiretroviral treatment (ART) by HIV-1 infected partners to suppress HIV-1 viral levels or as pre- exposure prophylaxis (PrEP) by HIV-1 uninfected partners, provide substantial (75-96%) protection against HIV-1 infection. These medications could form the cornerstone for a risk reduction intervention that would also include restricting unprotected sex to the most fertile days and the continued use of condoms during less fertile periods and once pregnancy is achieved. Through the proposed K99 period, the Candidate and her team will use existing data to 1) develop a pregnancy prediction model and scorecard to identify HIV-1 serodiscordant couples most likely to become pregnant and 2) estimate the efficacy of PrEP and ART to reduce HIV-1 transmission among HIV-1 serodiscordant couples with high pregnancy likelihood. Building on results from the K99 aims, in the R00 phase the Candidate and her team will 1) conduct mixed-methods data collection among participants in an established longitudinal cohort to determine the components of a feasible and accessible safer conception intervention and 2) design and pilot the new safer conception intervention among 40 research-nave HIV-1 serodiscordant couples. The final result of this research will be a coordinated, client- centered, evidence-based, risk reduction intervention to minimize the HIV-1 risk that couples face during peri- conception periods.